Endometriosis--Cannabinoids give symptom relief

Endometriosis-

Endometriosis is a condition in which the tissue that behaves like the cells lining the uterus (endometrium) grows in other areas of the body, causing pain, irregular bleeding, and possible infertility.
The tissue growth (implant) typically occurs in the pelvic area, outside of the uterus, on the ovaries, bowel, rectum, bladder, and the delicate lining of the pelvis. However, the implants can occur in other areas of the body, too.

Causes, incidence, and risk factors

Each month a woman's ovaries produce hormones that stimulate the cells of the uterine lining (endometrium) to multiply and prepare for a fertilized egg. The lining swells and gets thicker.
If these cells (called endometrial cells) grow outside the uterus, endometriosis results. Unlike cells normally found in the uterus that are shed during menstruation, the ones outside the uterus stay in place. They sometimes bleed a little bit, but they heal and are stimulated again during the next cycle.
This ongoing process leads to symptoms of endometriosis (pain) and can cause scars (adhesions) on the tubes, ovaries, and surrounding structures in the pelvis.
The cause of endometriosis is unknown, but there are a number of theories. One theory is that the endometrial cells loosened during menstruation may "back up" through the fallopian tubes into the pelvis. Once there, they implant and grow in the pelvic or abdominal cavities. This is called retrograde menstruation. This happens in many women, but there may be something different about the immune system in women who develop endometriosis compared to those who do not get the condition.
Endometriosis is a common problem. Sometimes, it may run in the family. Although endometriosis is typically diagnosed between ages 25 - 35, the condition probably begins about the time that regular menstruation begins.
A woman who has a mother or sister with endometriosis is six times more likely to develop endometriosis than women in the general population. Other possible risk factors include:
Starting menstruation at an early age
Never having had children
Frequent menstrual cycles
Periods that last 7 or more days
Problems such as a closed hyman, which blocks the flow of menstrual blood during the period

Symptoms

Pain is the main symptom for women with endometriosis. This can include:
Painful periods
Pain in the lower abdomen or pelvic cramps that can be felt for a week or two before menstruation
Pain in the lower abdomen felt during menstruation (the pain and cramps may be steady and dull or severe)
Pain during or following sexual intercourse
Pain with bowel movements
Pelvic or low back pain that may occur at any time during the menstrual cycle
Note: Often there are no symptoms. In fact, some women with severe cases of endometriosis have no pain at all, whereas some women with mild endometriosis have severe pain.

Other symptoms may be present, including:

• Constipation
• chronic fatigue
• heavy or long uncontrollable menstrual periods with small or large blood clots
• gastrointestinal problems including diarrhea, bloating and painful defecation
• extreme pain in legs and thighs
• back pain
• mild to extreme pain during intercourse
• pain from adhesions which may bind an ovary to the side of the pelvic wall, or they may extend between the bladder and the bowel,uterus, etc.
• extreme pain with or without the presence of menses
• premenstrual spotting
• mild to severe fever
• headaches
• depression
• hypoglycemia (low blood sugar)
• anxiety
In addition, women who are diagnosed with endometriosis may have gastrointestinal symptoms that mimic Irritable bowel syndrome.
Patients who rupture an endometriotic cyst may present with an acute abdomen as a medical emergency.
Occasionally pain may also occur in other regions. Cysts can occur in the bladder (although rare) and cause pain and even bleeding during urination. Endometriosis can invade the intestine and cause painful bowel movements or diarrhea.
In addition to pain during menstruation, the pain of endometriosis can occur at other times of the month and doesn't have to be just on the date on menses. There can be pain with ovulation, pain associated with adhesions, pain caused by inflammation in the pelvic cavity, pain during bowel movements and urination, during general bodily movement i.e. exercise, pain from standing or walking, and pain with intercourse. But the most desperate pain is usually with menstruation and many women dread having their periods. Also the pain can start a week before menses, during and even a week after menses, or it can be constant. There is no known cure for endometriosis.

Signs and tests

Tests that are done to diagnose endometriosis include:

Pelvic exam
Transvaginal ultrasound
Pelvic laparoscopy
Treatment
Treatment options include:
Medications to control pain
Medications to stop the endometriosis from getting worse
Surgery to remove the areas of endometriosis
Hysterectomy with removal of both ovaries
Treatment depends on the following factors:
Age
Severity of symptoms
Severity of disease
Whether you want children in the future
Some women who do not ever want children and have mild disease and symptoms may choose to just have regular exams every 6 - 12 months so the doctor can make sure the disease isn't getting worse. They may manage the symptoms by using:
• Exercise and relaxation techniques
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil) and naproxen (Aleve), acetaminophen (Tylenol), or prescription painkillers to relieve cramping and pain.
• Treatment may involve stopping the menstrual cycle and creating a state resembling pregnancy. This is called pseudopregnancy. It can help prevent the disease from getting worse. It's done using birth control pills containing estrogen and progesterone.
• You take the medicine continuously for 6 - 9 months before stopping the medicine for a week to have a period. Side effects include spotting of blood, breast tenderness, nausea, and other hormonal side effects.
• This type of therapy relieves most endometriosis symptoms, but it does not prevent scarring from the disease. It also does not reverse any physical changes that have already occurred.
• Another treatment involves progesterone pills or injections. Side effects may be bothersome and include depression, weight gain, and spotting of blood.
• Some women may be prescribed medicines that stop the ovaries from producing estrogen. These medicines are called gonadotropin agonist drugs and include nafarelin acetate (Synarel) and Depo Lupron.
• Potential side effects include menopausal symptoms such as hot flashes, vaginal dryness, mood changes, and early loss of calcium from the bones.
• Because of the bone density loss, this type of treatment is usually limited to 6 months. In some cases, it may be extended up to 1 year if small doses of estrogen and progesterone are given to reduce the bone weakening side effects.
• Surgery is an option for women who have severe pain that does not improve with hormone treatment, or who want to become pregnant either now or in the future.
• Pelvic laparoscopy or laparotomy is done to diagnose endometriosis and then remove or destroy all of endometriosis-related tissue and scar tissue (adhesions).
• Women with severe symptoms or disease who do not want children in the future may have surgery to remove the uterus (hysterectomy). One or both ovaries and fallopian tubes may also be removed. One out of three women who do not have both of their ovaries removed at the time of hysterectomy will have their symptoms return and will need to have surgery at a later time to remove the ovaries.

Cause

While the exact cause of endometriosis remains unknown, many theories have been presented to better understand and explain its development. These concepts do not necessarily exclude each other.Estrogens: Endometriosis is a condition that is estrogen-dependent and thus seen primarily during the reproductive years. In experimental models, estrogen is necessary to induce or maintain endometriosis. Medical therapy is often aimed at lowering estrogen levels to control the disease. Additionally, the current research into aromatase, an estrogen-synthesizing enzyme, has provided evidence as to why and how the disease persists after menopause and hysterectomy.Retrograde menstruation: The theory of retrograde menstruation, first proposed by John A. Sampson, suggests that during a woman's menstrual flow, some of the endometrial debris exits the uterus through the fallopian tubes and attaches itself to the peritoneal surface (the lining of the abdominal cavity) where it can proceed to invade the tissue as endometriosis. While most women may have some retrograde menstrual flow, typically their immune system is able to clear the debris and prevent implantation and growth of cells from this occurrence. However, in some patients, endometrial tissue transplanted by retrograde menstruation may be able to implant and establish itself as endometriosis.
Müllerianosis: A competing theory states that cells with the potential to become endometrial are laid down in tracts during embryonic development and organogenesis. These tracts follow the female reproductive (Mullerian) tract as it migrates caudally (downward) at 8–10 weeks of embryonic life. Primitive endometrial cells become dislocated from the migrating uterus and act like seeds or stem cells. This theory is supported by fetal autopsy.

Coelomic Metaplasia: This theory is based on the fact that coelomic epithelium is the common ancestor of endometrial and peritoneal cells and hypothesizes that later metaplasia (transformation) from one type of cell to the other is possible, perhaps triggered by inflammation.

Genetics: Hereditary factors play a role. It is well recognized that daughters or sisters of patients with endometriosis are at higher risk of developing endometriosis themselves; for example, low progesterone levels may be genetic, and may contribute to a hormone imbalance. There is an about 10-fold increased incidence in women with an affected first-degree relative. A 2005 study published in the American Journal of Human Genetics found a link between endometriosis and chromosome 10q26, while a 2010 Nature Genetics study detected a link with the 7p15.2 region.
Transplantation: It is accepted that in specific patients endometriosis can spread directly. Thus endometriosis has been found in abdominal incisional scars after surgery for endometriosis. It can also grow invasively into different tissue layers, i.e., from the cul-de-sac into the vagina. On rare occasions endometriosis may be transplanted by blood or by the lymphatic system into peripheral organs such as the lungs and brain.

Immune system: Research is focusing on the possibility that the immune system may not be able to cope with the cyclic onslaught of retrograde menstrual fluid. In this context there is interest in studying the relationship of endometriosis to autoimmune disease, allergic reactions, and the impact of toxins. It is still unclear what, if any, causal relationship exists between toxins, autoimmune disease, and endometriosis.

Environment: There is a growing suspicion that environmental factors may cause endometriosis, specifically some plastics and cooking with certain types of plastic containers with microwave ovens. Other sources suggest that pesticides and hormones in our food cause a hormone imbalance.

Birth Defect: In rare cases where imperforate hymen does not resolve itself prior to the first menstrual cycle and goes undetected, blood and endometrium are trapped within the uterus of the patient until such time as the problem is resolved by surgical incision. Many health care practitioners never encounter this defect, and due to the flu-like symptoms it is often misdiagnosed or overlooked until multiple menstrual cycles have passed. By the time a correct diagnosis has been made, endometrium and other fluids have filled the uterus and fallopian tubes with results similar to retrograde menstruation resulting in endometriosis. The initial stage of endometriosis may vary based on the time elapsed between onset and surgical procedure.

Epidemiology

Endometriosis can affect any female, from premenarche to postmenopause, regardless of race or ethnicity or whether or not they have had children. It is primarily a disease of the reproductive years. Estimates about its prevalence vary, but 5–10% is a reasonable number, more common in women with infertility (20–50%) and women with chronic pelvic pain (about 80%). As an estrogen-dependent process, it can persist beyond menopause and persists in up to 40% of patients following hysterectomy. In some cases, it may also begin beyond menopause ..

Treatments

While there is no cure for endometriosis, in many patients menopause (natural or surgical) will abate the process. Hormonal medication
Progesterone or Progestins: Progesterone counteracts estrogen and inhibits the growth of the endometrium. Such therapy can reduce or eliminate menstruation in a controlled and reversible fashion. Progestins are chemical variants of natural progesterone.
Avoiding products with xenoestrogens, which have a similar effect to naturally produced estrogen and can increase growth of the endometrium.
Hormone contraception therapy: Oral contraceptives reduce the menstrual pain associated with endometriosis. They may function by reducing or eliminating menstrual flow and providing estrogen support. Typically, it is a long-term approach. Recently Seasonale was FDA approved to reduce periods to 4 per year. Other OCPs have however been used like this off label for years. Continuous hormonal contraception consists of the use of combined oral contraceptive pills without the use of placebo pills, or the use of NuvaRing or the contraceptive patch without the break week. This eliminates monthly bleeding episodes.
Danazol (Danocrine) and gestrinone are suppressive steroids with some androgenic activity. Both agents inhibit the growth of endometriosis but their use remains limited as they may cause hirsutism and voice changes.
Gonadotropin Releasing Hormone (GnRH) agonist: These agents work by increasing the levels of GnRH. Consistent stimulation of the GnRH receptors results in downregulation, inducing a profound hypoestrogenism by decreasing FSH and LH levels. While effective in some patients, they induce unpleasant menopausal symptoms, and over time may lead to osteoporosis. To counteract such side effects some estrogen may have to be given back (add-back therapy). These drugs can only be used for six months at a time.
Lupron depo shot is a GnRH agonist and is used to lower the hormone levels in the woman's body to prevent or reduce growth of endometriosis. The injection is given in 2 different doses: a 3 month course of monthly injections, each with the dosage of (11.25 mg); or a 6 month course of monthly injections, each with the dosage of (3.75 mg).
Aromatase inhibitors are medications that block the formation of estrogen and have become of interest for researchers who are treating endometriosis
In patients in the reproductive years, endometriosis is merely managed: the goal is to provide pain relief, to restrict progression of the process, and to restore or preserve fertility where needed. In younger women with unfulfilled reproductive potential, surgical treatment attempts to remove endometrial tissue and preserving the ovaries without damaging normal tissue.

Procedures are classified as

• conservative when reproductive organs are retained,
• semi-conservative when ovarian function is allowed to continue,
Conservative therapy consists of the excision (called cystectomy) of the endometrium, adhesions, resection of endometriomas, and restoration of normal pelvic anatomy as much as is possible. There are combinations as well. A thin telescope-like instrument (the laparoscope) is placed into one incision, which allows the doctor to look for endometriosis using a small camera attached to the laparoscope. Small instruments are inserted through the incisions to remove the tissue and adhesions.
Semi-conservative therapy preserves a healthy appearing ovary, and yet, it also increases the risk of recurrence.
For patients with extreme pain, a presacral neurectomy may be indicated where the nerves to the uterus are cut.
After surgical treatment of deeply infiltrating endometriosis with colorectal involvement, a review study estimated the overall endometriosis recurrence rate to be approximately 10% (ranging between 5–25%)
Patients without infertility can be managed with hormonal medication that suppress the natural cycle and pain medication, while infertile patients may be treated expectantly after surgery, with fertility medication, or with IVF.

Other medication

NSAIDs: Anti-inflammatory. They are commonly used in conjunction with other therapy. For more severe cases narcotic prescription drugs may be used. NSAID injections can be helpful for severe pain or if stomach pain prevents oral NSAID use.
MST: Morphine sulphate tablets and other opioid painkillers work by mimicking the action of naturally occurring pain-reducing chemicals called "endorphins". There are different long acting and short acting medications that can be used alone or in combination to provide appropriate pain control.
Diclofenac in suppository or pill form. Taken to reduce inflammation and as an analgesic reducing pain.
Pentoxifylline, an immuno-modulatory agent

Recurrence

The underlying process that causes endometriosis may not stop after surgical or medical intervention. The most recent studies have shown that endometriosis recurs at a rate of 20 to 40 percent within five years following conservative surgery, unless hysterectomy is performed or menopause reached.
Vaginal childbirth decreases recurrence of endometriosis. In contrast, endometriosis recurrence rates have been shown to be higher in women who have not given birth vaginally, such as in Cesarean section

Complications of endometriosis include:

? Internal scarring
? Adhesions
? Pelvic cysts
? Chocolate cyst of ovaries
? Ruptured cyst
? Bowel obstruction
? Infertility
Other complications of endometriosis include bowel and ureteral obstruction resulting from pelvic adhesions. Peritonitis from bowel perforation can occur.
Ovarian endometriosis may complicate pregnancy. Active endometriosis produces inflammatory mediators that cause pain and inflammation, as well as scarring or fibrosis of surrounding tissue. Triggers of various kinds, including menses, toxins, and immune factors, may be necessary to start this process.
Pain can also occur from adhesions (internal scar tissue) binding internal organs to each other, causing organ dislocation. Fallopian tubes, ovaries, the uterus, the bowels, and the bladder can be bound together in ways that are painful on a daily basis, not just during menstrual periods.
Also, endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the central nervous system, potentially producing a variety of individual differences in pain that can, in some women, become independent of the disease itself.
Many women with infertility may have endometriosis. As endometriosis can lead to anatomical distortions.

Smoking

The risk of endometriosis has been reported to be reduced in smokers.

Aging

Aging brings with it many effects that may reduce fertility. Depletion over time of ovarian follicles affects menstrual regularity. Endometriosis has more time to produce scarring of the ovary and tubes so they cannot move freely or it can even replace ovarian follicular tissue if ovarian endometriosis persists and grows.
Endometriosis in postmenopausal women does occur and has been described as an aggressive form of this disease characterized by complete progesterone resistance and extraordinarily high levels of aromatase expression.

Co-morbidity

Endometriosis bears no relationship to endometrial cancer. Current research has demonstrated an association between endometriosis and certain types of cancers, notably ovarian cancer, non-Hodgkin's lymphoma and brain cancer. Endometriosis often also coexists with leiomyoma oradenomyosis, as well as autoimmune disorders. A 1988 survey conducted in the US found significantly more Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma in women with endometriosis compared to the general population.

Prognosis

Proper counseling of patients with endometriosis requires attention to several aspects of the disorder. Of primary importance is the initial operative staging of the disease to obtain adequate information on which to base future decisions about therapy. The patient's symptoms and desire for childbearing dictate appropriate therapy. Not all therapy works for all patients. Some patients have recurrences after surgery or pseudo-menopause. In most cases, treatment will give patients significant relief from pelvic pain and assist them in achieving pregnancy. It is important for patients to be continually in contact with their physician and keep an open dialog throughout treatment. This is a disease without a cure but with the proper communication, a woman with endometriosis can attempt to live a normal, functioning life.

Prevention

Use of combined oral contraceptives is associated with a reduced risk of endometriosis.

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